Abstract

Background

Arachidonic acid metabolite, generated by cyclooxygenase (COX), is implicated in the
colorectal cancer (CRC) pathogenesis. Inhibiting COX may therefore have anti-carcinogenic
effects. Results from use of non-steroidal anti-inflammatory drugs inhibiting only
COX have been conflicting. It has been postulated that this might result from the
shunting of arachidonic acid metabolism to the 5-lipoxygenase (5-LOX) pathway. Cancer
cell viability is promoted by 5-LOX through several mechanisms that are similar to
those of cyclooxygenase-2 (COX-2). Expression of 5-LOX is upregulated in colorectal
adenoma and cancer. The aim of this study was to investigate the shunting of arachidonic
acid metabolism to the 5-LOX pathway by cyclooxygenase inhibition and to determine
if this process antagonizes the anti-cancer effect in colorectal cancer cells.

Results

COX inhibitors suppressed PGE2 production but enhanced LTB4 secretion in COX-2 expressing cell lines (P <0.001). The level of COX-2 expression in colorectal cancer cells did not significantly
influence the anti-proliferative and pro-apoptotic effects of COX inhibitors due to
the shunting mechanism.

Conclusions

This study provides evidence of shunting between COX and 5-LOX pathways in the presence
of unilateral inhibition, and may explain the conflicting anti-carcinogenic effects
reported with use of COX inhibitors.